IE50102B1 - Polycarbonate/polyether copolymer membrane,a process for its preparation and use thereof - Google Patents

Abstract

A method is provided for producing a membrane from polycarbonate-polyether-blockcopolymers with about 5 to 35 weight percent of repeating alkyleneethercarbonate units and about 95 to 65 weight percent of repeating bisphenol A-carbonate units, wherein the polyethyleneoxide blocks have a molecular weight from about 1,000 to 20,000, wherein the intrinsic viscosity of the copolymer is from about 180 to 300 ml/g as measured in chloroform at 25 DEG C. and wherein the ultrafiltration rate is from about 4 to 200 ml/h.m2.mm Hg. In a first dissolving step a polycarbonate-polyether-copolymer is homogeneously mixed with a solvent at a temperature from about 80 DEG to 120 DEG C. and in a second dissolving step the temperature is brought to about 140 DEG to 180 DEG C. to produce a true solution. The filtered solution is cooled to from about 20 DEG to 50 DEG C. and is then extruded through a nozzle into a bath comprising a nonsolvent for the polymer for precipitating the polymer. The precipitated polymer is then washed and dried. The resulting membranes improve the processes of hemodialyzing and of homofiltration.

Description

This invention relates to a membrane in the form of a flat film, tubular film or hollow filament of a polycarbonate/polyether block copolymer with 5 to 35% by weight of recurring alkylene ether carbonate units and 95 to 65% by weight of recurring bisphenol A carbonate units.

Such membranes are already known. Thus, German Offenlegungsschrift 2,713,283 describes a polycarbonate/ polyether block copolymer membrane, the properties of which are largely directed so that the membrane has a relatively high dialytic permeability for Vitamin B 12 at a low rate of ultrafiltration. The intrinsic viscosities resulting from the molecular weights indicated are less than 170 ml/g, and values of below 4 ml/hour.m . mm Hg are said to be maintained for the rate of ultrafiltration.

The mechanical properties of such membranes are not very satisfactory.

Haemofiltration has recently been introduced as a treatment method for dialysis patients suffering from high blood pressure. Membranes which have a high hydraulic permeability are required for the dialysis treatment, for reinfusion of relatively large amounts of liquid into the human blood circulation.

Membranes have hitherto been produced from polycarbonate/polyether copolymers (compare, for example, U.S. Patent Specification 4,048,271 and German Offenlegungsschrift 2,711,498) by spreading a dilute polymer solution containing a substance for the formation of pores Onto a surface by means of a knife and then evaporating off some of the solvent. After evaporating off some of the solvent, the membranes were then gelled in a water bath. After washing, the membranes were stored in a plastic bag or in another receptacle which contained water and a sterilising agent (for exanple formaldehyde).

U.S. Patent Specification 4 160 791 discloses membranes of polycarbonate/polyether block copolymers, which are formed by the phase inversion process and are accordingly asymmetric membranes. Because of their structure, asymmetric membranes possess a skin. The dialysis properties show that the permeability to vitamin B12 substantially rises with the rate of ultrafiltration.

The membrane described in U.S. Patent Specification 4 160 791 is not subjected to any drying, but is stored in a welded polyethylene bag with addition of formaldehyde.

DE-AS 11 62 559 discloses the use of polycarbonate/ polyether copolymers for manufacturing foils, threads and fibres. The foils are said to be extruded from solutions.

In general, however, extruded foils have no membrane properties, unless special measures are observed during extrusion.

The present invention had the objective of providing membranes which are produced from polycarbonate/polyether copolymers and which have a high ultrafiltration capacity and mechanical properties such that they can be stored and handled in the dry state. The object of the invention also consisted in producing such membranes directly in a technologically simplified process.

The invention accordingly provides a membrane in the form of a flat film, tubular film or hollow filament of a polycarbonate/polyether block copolymer with 5 to 35% by weight of recurring alkylene ether carbonate units and 95 to 65% by weight of recurring bisphenol A carbonate units, wherein the polyether blocks are polyethylene oxide blocks with an average molecular weight of 1,000 to 20,000,the structure of the membrane being isotropic and skin-free, the intrinsic viscosity of the copolymer is 180 to 300 ml/g (measured in chloroform at 25°C) and the ultrafiltration rate is 4 to 200 ml/hour, m. .mm Hg and the membrane is produced by the extrusion of a solution of the polycarbonate/polyether block copolymer in γ-butyrolactone in a non-solvent.

The rate of ultrafiltration through the membranes is determined by measuring the volume of liquid which passes through the membranes under a given pressure difference, at a temperature of 20°C and through a membrane area fixed by the particular apparatus, and which is standardised to unit area, unit time and unit pressure for general comparability. Water is used as the liquid. 80103 The method is described in Evaluation of Hemodialyzers and Dialysis Membranes by the U.S. Department of Health, Education and Welfare, DHEW Publication No (NIH) 77 1294, pages 24 - 26.

The numerical value of the dialytic permeability DLB12 °£ t^ie meit|brane according to the invention for Vitamin B 12 (measured at 20°C), as a function of the ultrafiltration capacity, is in each case preferably given by DLB^2 ~ 12.5 + 0.25) /UFC. The ultrafiltration capacity has the dimensions ml/minute. kp. The ultrafiltration capacity is obtained from the rate of ultra2 filtration in ml/hour.m .mm Hg by dividing by the factor 2 815, that is to say a UFR of, for example, 4 ml/h.m .mm Hg corresponds to UFC of 4.9. 10 ml/minute. kp. The connection between the UFC and the dialytic permeability ' 50102 for Vitamin B 12 (DLg12) given as a formula applies only fran a numerical point of view and not in the dimensions. It was determined by regression.

The dialytic permeability of dialysis membranes is a measure of the permeability of the membranes to dissolved substances and depends on the molecular weight of the dissolved substances, as well as on the membrane.

As a test substance for uraemia poisons of an average molecular weight in the region 500 - 3,000, a solution of 100 mg/1 of Vitamin B 12 is used to determine the mean molecular permeability in order to assess the suitability of a membrane. The diffusive change in concentration, with respect to time and in the absence of applied pressure, of two starting solutions of different concentra15 tions on either side of the membrane is measured. If a Vitamin B 12 solution is used, the mean molecular permeability is then calculated according to the following equation. lnAC1/4C2 Mean molecular permeabiltiy = A(lZVa + ^Vb) (t2-t1) 2o ACi = difference in concentration measured between the two sides of the membrane at time t^ A = membrane area Va and Vb = volumes of the two chambers separated by the membrane.

The method is also described in Evaluation of Hemodialyzers and Dialysis Membranes of the U.S. Department of Health, Education and Welfare, DHEW Publication No.

(NIH) 77-1294, pages 14 and 15, for measurement in the case of flat membranes and tubular membranes, and page 20, for measurement of hollow filaments.

In a particular embodiment of the invention the polycarbonate/polyether copolymer is built up from 7 to 13% by weight of recurring polyethylene oxide carbonate units and 93 to 87% by weight of recurring bisphenol A carbonate units and the average molecular weight of the polyethylene oxide blocks is 6,000 to 10,000. The average molecular weight is to be understood as the weighted average.

Such a membrane can advantageously be dried in the absence of any after-treatment agents, such as, for example, glycerol, without the structure of the membrane collapsing. The membrane is characterised in that it contains less than 0.5% by weight of auxiliaries and foreign substances.

The structure of such membranes can be influenced in an advantageous manner to the effect that they have an even higher rate of ultrafiltration in relation to the Vitamin B 12 permeability. The numerical value of the dialytfc permeability DLB12 of such a membrane for Vitamin B 12 (measured at 20°C), as a function of the ultrafiltration capacity, is in each case preferably given by DL The invention also provides a process for the production of a membrane in the form of a flat film, tubular film or hollow filament, in which process a polycarbonate/ polyether block copolymer is homogeneously mixed with γ-butyrolactone at a temperature of 80 to 120°C in a first dissolving stage, the mixture is then converted into a true solution at 140 to 180°C in less than 10 minutes in a second dissolving stage and, after filtration, the solution is cooled to 20 to 50°C, and this solution is extruded through a die into a bath containing a nonsolvent for the polymer so as to give a tubular film, flat film or hollow filament and this extruded material is washed with the aid of washing baths and treatment baths until free from solvent, to the limit of detection, and is dried under conditions which prevent shrinkage in the longitudinal and transverse dimensions.

The customary sheet dies and annular dies, such as are known, for example, from the production of flat films and tubular films by the Cuoxam process, are used for flat films and tubular films. Customary hollow filament dies, such as are described, for example in German Patent Specification 736,721 are used for hollow filaments. Butyl stearate has proved particularly suitable as the cavity-forming liquid. Other inert liquids can be used in the same manner. The dies are S0102 in general immersed in the bath which contains the nonsolvent. However, it is also possible to allow the polymer solution to flow initially through an air zone, e.g. in order to be able to use larger die dimensions.

While cast films are frequently formed from relatively dilute polymer solutions by evaporating off some of the solvent, relatively concentrated solutions are used in the process according to the invention.

The polycarbonate/polyether block copolymers and γ-butyro10 lactone are preferably mixed in a weight ratio in the range 10 : 90 to 20 : 80 in the first dissolving stage.

By using γ-butyrolactone as the solvent and by precipitating in a non-solvent, it is possible, surprisingly, to obtain porous membranes which have out15 standing mechanical properties coupled with good dialysis and ultrafiltration capacities without any auxiliaries which influence the structure being required initially.

A wide range of structures can be established in the desired manner by the process conditions.

Sufficiently rapid transition of the mixture of γ-butyrolactone and polycarbonate/polyether copolymer into a homogeneous, gelatinous mixture is achieved if, preferably, the temperature in the first dissolving stage is 100 to 110°C.

The temperature in the second dissolving stage should not exceed 18O°C, bec.iUKP otherwise I here in (he danger of damage to the copolymer by heat, which leads to adverse properties of the membrane. Tho transition, intended in this dissolving stage, of a gelatinous solution such as is obtained in the first dissolving stage, into a true solution, is ensured, with a relatively short residence time, if the temperature is the second dissolving stage is 150 - 170°C.

Non-solvents in the context of the invention are those liquids in which the copolymer is insoluble and which are miscible with the solvent γ-butyrolactone in all proportions.

These liquids include, for example, low-boiling ketones and ethyl lactate.

A preferred non-solvent is water, which is outstandingly suitable.

Other preferred non-solvents are alcohols, amongst which ethyl alcohol is particularly preferred because toxicity as a result of residual traces of alcohol need not be feared in the case of this alcohol, whereas this danger cannot be excluded in the case of methyl alcohol.

The non-solvents can contain additives, such as, for example, salts and other electrolytes, glycerol and butyrolactone.

Washing baths and treatment baths are those which contain a non-solvent as the essential constituent. In general, the membrane is treated with an aqueous or alcoholic glycerol solution in a final treatment bath. However, the glycerol solution can also advantageously be sprayed on or printed on.

It is essential that the membrane is dried under conditions which prevent shrinkage in the longitudinal and transverse dimensions. This means that when flat films and tubular films are dried, only the thickness of the membrane should change, not the surface area of the membrane. In the drying of hollow filaments, the internal diameter and length do not change because they are prevented from doing so by the cavity-forming liquid and the filament tension on passage through a drier.

Flat films are preferably dried on a belt circulating in a drier.

Prevention of shrinkage can be achieved by fixing the sides of the film to the belt, for example by clamping devices. Adhesion of the membrane film onto the belt results in a particularly favourable form of prevention of shrinkage. The membrane film is kept so firmly on the entire surface of the belt by adhesion that it cannot shrink in the longitudinal direction or in the transverse direction. After drying, it can be removed from the belt in a simple manner.

The material from which the belt has been made and the naLure of the surface of the belt are criteria for its effectiveness. A belt made of polyethylene terephathalate film has proved very suitable.

The invention is illustrated in more detail with the aid of the following examples: 2.325 kg of a polycarbonate/polyether copolymer w.iich contains bisphenol A and polyethylene glycol with an average molecular weight of 10,000 in a weight ratio of 90% : 10%, calculated as carbonate units, and which has an intrinsic viscosity of 200 is added, at about room temperature and with high-speed stirring, to 15.55 kg of γ-butyrolactone, so that the concentration 13%, in a 1 tank which can be heated and has a stirrer. The mixture is warmed to 100 - 110°C, whereupon a solution which is still gelatinuous is formed. The solution is degassed in vacuo and passed to a homogenising step in a dynamic mixer by means of two gear pumps, of which one operates as a pressure pump and the other as a metering pump. The solution is then heated to about 160°C in a pipeline which can be heated and has a double-wall jacket, whereupon a clear, gel-free solution is formed. Static mixing organs are incorporated into the pipeline for better heat transfer. The residence time in this heating zone is 7 minutes. The hot solution then passes to a filtering unit. where it is filtered through layers of fabric. It is then cooled to temperatures below +50°C in a cooling zone and subjected to fine filtration, in-line, through a 2 urn metal fabric filter. The clear, degassed and filtered casting solution, which has a kinematic viscosity of 92.5 Pa.s at 20°C, then passes to a sheet die of which the slit width is 50 cm and the gap is adjusted to 120 ym.

A membrane which has a wet thickness of about 40 pm and which, over the thickness, exhibits no significant differences in structure under a transmission electron microscope, even at a magnification of 80,000 : 1, and can thus be designated isotropic is formed by precipitation in water of room temperature. It should also be stated that the dialytic and ultrafiltration properties of the membranes thus formed are not determined by a type of skin on the surfaces but by the overall precipitated structure. The membranes thus obtained are freed from γ-butyrolactone, to below the detection limit in a gas chromatograph, by washing in a washing zone, and are then converted into the dry state.

Drying is in general effected in the manner described below.

The membranes, which are still wet from production, are passed through a bath which has a temperature of 25°C and contains, for example, 35¾ of glycerol, 10¾ of' water and 55¾ of ethyl alcohol. The residence time is about 1 minute. After leaving the bath, the membrane is passed through a pair of rollers in order to ensure a thorough wiping of the surface of the membrane and is then placed on the surface of an impermeable belt which circulates in a drying tunnel and must be of such a nature that the membrane firmly adheres to the substrate during the entire drying process and can shrink neither in the longitudinal direction nor in the transverse direction.

A drying process without this prevention of shrinkage always leads to a drastic reduction in the performance data for the membrane. After drying, the membrane must be easily detachable from the belt substrate. Polyethylene terephthalate film (obtainable under the tradename Melinex) has been used as the belt material.

However, other films, for example also metal foils with a defined peak-to-valley height, can also be used here.

The wet membrane can also be dried immediately, without having first been passed through a bath of glycerol, water and ethyl alcohol, in an otherwise identical manner, independently of the composition of the polymer.

There is no need to fear that removal of the water from the membrane material leads to collapse of the membrane and that the performance data of the membranes are severely adversely affected.

The composition of the polymer used for producing the membrane is critical for selecting the process, and in part ieul.ir, the type oi drying last described is possible with polycarbonate/polyether copolymers of 7 to 13¾ by weight of recurring polyethylene oxide carbonate units and 93 to 87 by weight of recurring bisphenol A carbonate units in which the polyethylene oxide blocks have an average molecular weight of 6,000 to 10,000.

The dried membranes according to the invention were then sterilised by irradiation with γ-rays, for example from a Co-60 source of radiation. It was found, surprisingly, that the tensile strength in the longitudinal direction had risen by about 50%, from about 800 cN to over 1,200 cN, and the elongation of the membrane material had risen from 100% to 430 - 500%, that is to say to about 4 to 5 times the value, after irradiation with 2.5 Mrad. The measurements were made on samples 100 mm long with a clamped width of 15 mm and a rate of elongation of 500 mm/minute, using a Zwick apparatus.

The results of measurements on various mambranes according to the invention are summarised in the following tables.

Table 1 shows the dependence of the UFC on the polymer composition and various influential parameters in the production of the membrane.

Table II shows the results measured on some of these membranes (a) after immediate drying at 60°C and a residence time of 3 minutes in the drier without prior after-treatment.

Table III shows the results measured on the membranes listed in Table I after drying with prior after5 treatment. The residence time in the drier is likewise minutes in each case.

With the aid of measurements of the dialytic permeability to inulin (MW = 5,200) and Cytochrome C (MW 13,500), it was established that the exclusion limit of the membranes according to the invention is at a molecular weight of about 10,000.

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Serial No. Table III DL 12-103 (dry membrane) [cm/minute] Membrane thickness (dry) [pm] UPC.103 (dry) [ml/minute.kp[ 5 b 24 7.2 5.6 10 b 20 71.1 13.0 15 b 18 12.1 8.7 15 c 19 19.9 11.7 b = after-treatment with glycerol/water/ethanol in a ratio of 35%:10%:55% at a bath temperature of 25°C before drying. Drier temperature: 60°C. c = after-treatment with glycerol/water/ethanol in a ratio of 41%:9%:50% at a bath temperature of 25°C before drying. Drier temperarure: 5O°C.

Claims (5)

1. -5 for haemofiltration. 1-5 for haemodialysis. 20. The use of a membrane according to any one of Claims

1. A membrane in the form of a flat film, tubular film or hollow filament of a polycarbonate/polyether block copolymer with 5 to 35% by weight of recurring alkylene ether carbonate units and 95 to 65% by weight of recurring bisphenol A carbonate units, wherein the polyether blocks are polyethylene oxide blocks with an average molecular weight of 1,000 to 20,000, the structure of the membrane being isotropic and skin-free, the intrinsic viscosity of the copolymer is 180 to 300 ml/g (measured in chloroform at 25°C) and the ultrafiltration rate is 4 to 200 ml/hour.m .mm Hg and the membrane is produced by the extrusion of a solution of the polycarbonate/polyether block copolymer in γ-butyrolactone in a non-solvent.

2. A membrane as claimed in Claim 1, wherein the numerical value of the dialytic permeability DL B12 for Vitamin B 12 (measured at 20°C), as a function of the ultrafiltration capacity, is given by DL B ^ 2 = (2.5 - 0.25) χ/OFC.

3. A membrane as claimed in Claim 1, wherein the polycarbonate/polyether copolymer is built up from 7 to 13% by weight of recurring polyethylene oxide carbonate units and 93 to 87% by weight of recurring bisphenol A carbonate units, and the average molecular weight of the polyethylene oxide blocks is 6,000 to 10,000.

4. A membrane as claimed in Claim 3, which comprises less than 0.5% by weight of auxiliaries and foreign substances. 5. A membrane as claimed in Claim 4, wherein the numerical value of the dialytic permeability DL B ^ 2 for Vitamin B 12 S0102 (measured at 2O°C), as a function of the ultrafiltration capacity, is given by = “ 0.2) JOFC. 6. A process for the production of a membrane according to any one of Claims 1-5 wherein a polycarbonate/polyether block copolymer is homogeneously mixed with γ-butyrolactone at a temperature of 80 to 120° C in a first dissolving stage, the mixture is then converted into a true solution at 140 to 180°C in less than 10 minutes in a second dissolving stage and, after filtration, the solution is cooled to 20 to 50°C, and this solution is extruded through a die into a bath containing a non-solvent for the polymer to give a tubular film, flat film or hollow filament and this extruded material is washed with the aid of washing baths and treatment baths until free from solvent, to the limit of detection, and is dried under conditions which prevent shrinkage in the longitudinal and transverse dimensions. 7. A process as claimed in Claim 6, wherein the polycarbonate/ polyether block copolymer and γ-butyrolactone are mixed in 20 a weight ratioyPthe range 10 : 90 to 20 : 80. 8. A process as claimed in Claim 6 or Claim 7, wherein the temperature in the first dissolving stage is 100 to 110°C. 9. Λ process as claimed in any of claims 6 to 8, wherein the temperature in the second dissolving stage is 15O-17O°C. 10. A process as claimed in any of Claims 6 to 9, wherein water is employed as the non-solvent. 5 11. A process as claimed in any of claims 6 to 9, wherein alcohols are employed as the non-solvents. 12. A process as claimed in any of Claims 6 to 11, wherein the non-solvent contains additives. 13. A process as claimed in any of Claims 6 to 12, wherein, 10 for the production of a flat film membrane, the wet, solventfree washed film is dried on a belt circulating in a drier. 14. A process as claimed in Claim 13, wherein prevention of shrinkage is achieved by fixing the sides of the film to the belt. 15 15. A process as claimed in Claim 13, wherein prevention of shrinkage is achieved by adhesion of the membrane film onto the belt. 16. A process as claimed in Claim 15, wherein the belt consists of polyethylene terephthalate film. 20 17. A process of haemodialysis is wherein a membrane as claimed in any of Claims 1 to 16 is used. 18. A process of haemofiltration wherein a membrane as claimed in any of Claims 1 to 16 is used. 30102 19. The use of a membrane according to any one of Claims

5. 21. A process as claimed in Claim 6, substantially as hereinbefore described.